The invention relates to the labeling, such as with radio pharmaceuticals, fluorescence emitting compounds or other probe detectable materials, of diseased or malfunctioning candidate cells for subsequent treatment with a medicinal compound, the identification in situ of the candidate cells using a probe sensitive to the presence of the label and then treatment of the identified cell. Alternatively, normal tissue may be label such that diseased tissue appears as a cold (unlabeled) spot. Still further, certain tissue may be labeled with a certain radioisotope or fluorescing compound while other tissue is labeled with a different detectable material so the different tissue provides a different emission, i.e. beta versus gamma radiating radioisotopes, or two radioisotopes emitting gamma rays with different energies or radiation versus florescence emissions. A further variation involves using a radiolabeled treatment medium which is applied to labeled or unlabeled tissue. The efficacy of the delivery technique and treatment effectiveness can then be monitored. If labeled treatment medium is delivered to labeled tissue, it is preferred that different radioisotope, fluorescence or otherwise detectable material be used for labeling the tissue and treatment medium. However, the same labeling material can be used and effectiveness determined based on the enhancement of the radiation count from the target tissue. While the inventions described below are primarily discussed using radiolabeling in conjunction with suitable radiation detectors, other labeling, such as fluorescence labeling with optical sensors can be used as alternate approaches. One skilled in the art will recognize that other detectable labeling and suitable detection probes can be used in the inventive devices and procedures described herein.
Addressed are improved instruments with enhanced operability, controllability, diagnostic capability and treatment capability. For example, the described devices can be used in an MRI environment, can provide a visual image as well as a radiation image, allow 3D tracking of the probe's position and direction correlating with tomographic images taken before surgery, provide a controllable field of view, and allow delivery of treatment compounds which themselves may be radiolabeled, which may have probe detectable labels, to the disease tissue rather than surrounding normal tissue, or vice versa, while the probe is at the site of the labeled cells. A determination can then be made as to whether the treatment compounds have in fact been incorporated into the target tissue. Subsequent diagnostic use of the probes at the same body site can also determine if the diseased tissue has been replaced in whole or in part by normal tissue as well as the extend of replacement or healing at the treatment site.
In one embodiment, the invention relates to in situ gene therapy using a beta or gamma radiation detection probe to locate radio-labeled cells, also referred to as candidate cells, and the delivery of corrective or therapeutic genes to the candidate cells identified by the radiation detection probe while the probe is positioned adjacent to the labeled and located cells. Other treatment modalities involve the identification of vulnerable plaque in atherosclerotic vessels, treatment of that plaque and the subsequent determination of the efficacy of the treatment. A still further treatment modality involves the location of diseased myocardial tissue in the heart using specific radiotracers, delivery of a treatment composition directly to that tissue and the subsequent evaluation of efficacy of that treatment.
Devices for use in the procedures contemplated by the invention herein include, but are not limited to, intraoperative radiation detection probes, intraoperative radiation imaging probes, catheter mounted radiation detection probes and probes attached to surgical gloves so that the probe tip can be manually manipulated by the physician and placed adjacent to suspect tissue at an operative site. These probes carry one or more radiation detectors. This includes the use of different detectors (i.e. gamma and beta detectors) on a single probe or the use of two different probes delivered simultaneously or serially to the targeted site. Reference to radiation is not limited to nuclear radiation but also includes optical radiation (fluorescence, phosphorescence, including UV, visible or IR emissions) and related detectors and transmission devices.